Fanconi anemia is a genetic condition that is inherited in an autosomal recessive manner. This rare disorder affects around 1000 individuals worldwide. To date, sixteen genes have been associated with the condition and these include:

• FANCA
• FANCB
• FANCC
• FANCD1
• FANCD2
• FANCE
• FANCF
• FANCG
• FANCI
• FANCJ
• FANCL
• FANCM and
• FANCN

An autosomal recessive inheritance pattern, means one mutated allele for the condition needs to be passed on from each parent for their offspring to develop the condition. Each child then has a 25% risk of developing the condition. Of the genes that have been linked to Fanconi anemia, FANCB is the only exception to the condition being autosomal recessive, as this gene is found on the X chromosome and the pattern of inheritance is therefore X-linked.

Ashkenazi Jews and Afrikaners are at a greater risk of this genetic condition than other ethnicities.

Molecular basis of the disease

Fanconi anemia affects DNA repair enzymes, which predisposes affected individuals to cancer. The genes involved in this condition code for proteins involved in the recognition and repair of DNA and mutations in these genes means cells continue to live even though they contain damaged DNA.

Research has shown that eight of the proteins (FANC-A, -B, -C, -E, -F, -G, -L and -M) form a complex that moves from the cytoplasm into the nucleus in response to DNA damage. The assembly of the proteins is activated when FANCM detects the DNA damage and after assembly, the complex induces FANCL to act as a E3 ubiquitin-ligase and monoubiquitinate FANCD2. Monoubiquitinated FANCD2 then interacts with the BRCA1/BRCA2 complex. BRCA1 and BRCA2 re important genes that code for tumor suppressor proteins.